Left Ventricular Biopsy in the Diagnosis of Myocardial Diseases
2018; Lippincott Williams & Wilkins; Volume: 137; Issue: 10 Linguagem: Inglês
10.1161/circulationaha.117.030834
ISSN1524-4539
AutoresNorbert Frey, Benjamin Meder, Hugo A. Katus,
Tópico(s)Cardiomyopathy and Myosin Studies
ResumoHomeCirculationVol. 137, No. 10Left Ventricular Biopsy in the Diagnosis of Myocardial Diseases Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessArticle CommentaryPDF/EPUBLeft Ventricular Biopsy in the Diagnosis of Myocardial Diseases Norbert Frey, MD, Benjamin Meder, MD and Hugo A. Katus, MD Norbert FreyNorbert Frey Department of Internal Medicine III (Cardiology and Angiology), University Hospital Schleswig-Holstein, Campus Kiel, Germany (N.F.). German Centre for Cardiovascular Research, partner site Hamburg/Kiel/Lübeck, Germany (N.F.). , Benjamin MederBenjamin Meder Institute for Cardiomyopathies Heidelberg and Department of Internal Medicine III, University of Heidelberg, Germany (B.M., H.A.K.). German Centre for Cardiovascular Research, partner site Heidelberg/Mannheim, Germany (B.M., H.A.K.). and Hugo A. KatusHugo A. Katus Institute for Cardiomyopathies Heidelberg and Department of Internal Medicine III, University of Heidelberg, Germany (B.M., H.A.K.). German Centre for Cardiovascular Research, partner site Heidelberg/Mannheim, Germany (B.M., H.A.K.). Originally published6 Mar 2018https://doi.org/10.1161/CIRCULATIONAHA.117.030834Circulation. 2018;137:993–995Myocardial biopsies have been performed as early as 1956, initially via transthoracic needle, and in 1962 for the first time in a transvenous approach. A consensus statement of the American Heart Association, American College of Cardiology, and European Society of Cardiology endorsed the acquisition of biopsies in several clinical scenarios in which biopsy-guided diagnostics can identify a treatable specific cause. Hence, a Class I indication (Evidence Level B) was ascribed to cases with new onset of unexplained heart failure with hemodynamic compromise, heart failure with ventricular arrhythmia or conduction disease, and heart failure unresponsive to conventional treatment, respectively.1 Eleven other clinical scenarios including the diagnostic workup of "stable" cardiomyopathies have been assigned Class IIa/IIb recommendations. It is important to note that this scientific statement has not been updated since 2007. Thus, the potential contribution of advanced molecular diagnostics of tissue samples in a precision medicine approach has not yet been considered.Indications, Type of Biopsy, and Access RouteTraditionally, endomyocardial biopsies (EMBs) have been obtained from the right ventricle (RV) via central venous access. While seemingly easier, this strategy appears counterintuitive because the clinical consequences of many relevant pathologies affect predominantly the left ventricle (LV), for example, in most cases of cardiomyopathy or myocarditis. For instance, in sarcoidosis, granulomas are less frequently located in the RV, which lowers the sensitivity of diagnosing this treatable condition. Indeed, larger case series showed that the diagnostic yield of LV biopsies is higher than RV tissue samples. Yilmaz et al2 demonstrated a higher yield for detection of myocarditis in LV or biventricular EMBs than in RV biopsies alone. The same finding was noted in a recent retrospective series of 136 patients in which the sensitivity of LV biopsies was 3-fold higher than that of RV biopsies. Chimenti and Frustaci3 reported that in patients subjected to biventricular EMBs, LV samples revealed diagnostic clues in 96.3% of cases (2307 patients) versus 71.4% (1711 patients) in RV tissue (P<0.001). In the context of myocarditis, the most frequent finding was lymphocytic infiltration (95.5%), followed by eosinophilic infiltrates (3.6%) or giant cells/sarcoidosis granulomas (together 0.9%). Of note, in this study, LV biopsy also had a better safety profile than RV biopsy, although LV EMBs were taken mainly from the seemingly more risk-prone free wall and RV EMBs from the septum.To further improve sensitivity, noninvasive imaging techniques or electroanatomic mapping may be used to identify disease-affected myocardial regions. Cardiac magnetic resonance imaging can increase the sensitivity for the detection of giant cell myocarditis by advising for RV or LV biopsy according to the distribution of inflammatory regions in the LV.4 This strategy is likely transferable to other myocardial diseases and may be performed by real-time magnetic resonance imaging–guided EMBs in the future. To reach the location of interest, deflectable guide catheters are already available and can be used in conjunction with traditional bioptomes. Here, echocardiographic imaging is needed to avoid injury of the leaflets and cordae.Besides the appropriate selection of the site of biopsy, the number of biopsy particles determines the diagnostic yield. At least 3 to 5 samples from different regions should be obtained, and detailed workup, including immunohistochemistry and molecular analysis (virus polymerase chain reaction), should be considered. Electron microscopy can contribute in selected cases of mitochondrial or storage disease, some of which are treatable, for example, by enzyme replacement therapy.More recently, radial access has emerged as the preferred route for coronary diagnostics and interventions and also appears attractive to obtain myocardial biopsies. In fact, it has been shown that with the use of modern techniques and material such as 6F and sheathless guiding catheters, LV biopsies can be performed safely and with a high success rate via radial access. This procedural progress may facilitate the implementation and acceptance of LV biopsies as standard procedure in the diagnostic workup of patients with cardiomyopathy and myocarditis.SafetyIn experienced hands, the acquisition of EMB appears to be safe with a rate of major complications of <1%,3 which is also the case in our centers. There are few data supporting the common thinking that RV biopsies can be acquired more safely than LV biopsies. For example, pericardial effusion with or without cardiac tamponade is even more frequent in RV compared with LV biopsy. It has to be taken into account, however, that most of the literature on procedure-related complications is reported from centers with extensive experience, raising the concern of potentially higher complication rates in less experienced settings. Specific safety considerations apply to the acquisition of EMB from the LV. To avoid air embolism to the brain, back-bleeding through the guiding catheter must be guaranteed between each single biopsy taking. Arterial access site complications may be largely avoided by a transradial approach. Taken together, the current literature is consistent in showing a very acceptable safety profile for LV biopsy.Molecular Research and DiagnosticsResearch on targeted therapeutic concepts against heart failure and cardiomyopathy is hampered by the lack of available myocardial tissue. In recent years, the technological advances have enabled deeper insights into the transcriptional and epigenetic alterations in living patients, for example, shedding light on complex patterns of epigenetic networks in heart failure.5 In a study by Meder et al,5 mapping of epigenetic DNA methylation, mRNA transcription, and genome sequencing revealed reprogramming of gene-regulatory networks during heart failure, involving evolutionary conserved cardiac stress-signaling proxies (eg, ANP and BNP loci) and developmental genes (eg, TBX5, HAND2). Although this study relied on LV biopsy samples of cases and controls, the comparison of epigenetic patterns of RV and LV tissue revealed recently that there are overlapping (CTCF repressor sites) but also differential methylation (transcription factor binding sites) signals. Hence, also on the molecular level, LV and RV samples show distinct fingerprints. The understanding of these networks will likely improve diagnostics and substratification of the disease. A broader use of EMBs, especially from the LV, would likely also propel innovative studies on the translatome, metabolome, and proteome of the diseased heart and could eventually lead to the identification of novel treatment targets.Summary and OutlookThe analysis of myocardial biopsies is recommended and required for treatment decisions in specific disease entities. Although progress in noninvasive diagnostics such as cardiac magnetic resonance imaging and biomarkers will further improve clinical phenotyping, we believe that for a personalized precision medicine approach in patients with cardiomyopathy and myocarditis, data from the affected organ are needed, which can be derived only from sophisticated molecular analyses of myocardial tissue. This will likely require myocardial tissue investigations with state-of-the-art methods in immunohistochemistry, molecular virology, transcriptomics, epigenomics, and even single-cell molecular analyses. Targeted biopsies, preferably from the LV and acquired via radial access with low risk, will be an important tool in this context.DisclosuresNone.Footnotes*Drs Frey and Meder contributed equally.The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.http://circ.ahajournals.orgNorbert Frey, MD, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Innere Medizin III, Arnold-Heller-Straße 3, Haus 6, D-24105, Germany. E-mail [email protected]References1. Cooper LT, Baughman KL, Feldman AM, Frustaci A, Jessup M, Kuhl U, Levine GN, Narula J, Starling RC, Towbin J, Virmani R, American Heart Association, American College of Cardiology, European Society of Cardiology, Heart Failure Society of American, and Heart Failure Association of the European Society of Cardiology. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology: endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology.Circulation. 2007; 116:2216–2233.LinkGoogle Scholar2. Yilmaz A, Kindermann I, Kindermann M, Mahfoud F, Ukena C, Athanasiadis A, Hill S, Mahrholdt H, Voehringer M, Schieber M, Klingel K, Kandolf R, Böhm M, Sechtem U. Comparative evaluation of left and right ventricular endomyocardial biopsy: differences in complication rate and diagnostic performance.Circulation. 2010; 122:900–909. doi: 10.1161/CIRCULATIONAHA.109.924167.LinkGoogle Scholar3. Chimenti C, Frustaci A. Contribution and risks of left ventricular endomyocardial biopsy in patients with cardiomyopathies: a retrospective study over a 28-year period.Circulation. 2013; 128:1531–1541. doi: 10.1161/CIRCULATIONAHA.13.001414.LinkGoogle Scholar4. Unterberg-Buchwald C, Ritter CO, Reupke V, Wilke RN, Stadelmann C, Steinmetz M, Schuster A, Hasenfuß G, Lotz J, Uecker M. Targeted endomyocardial biopsy guided by real-time cardiovascular magnetic resonance.J Cardiovasc Magn Reson. 2017; 19:45. doi: 10.1186/s12968-017-0357-3.CrossrefMedlineGoogle Scholar5. Meder B, Haas J, Sedaghat-Hamedani F, Kayvanpour E, Frese K, Lai A, Nietsch R, Scheiner C, Mester S, Bordalo DM, Amr A, Dietrich C, Pils D, Siede D, Hund H, Bauer A, Holzer DB, Ruhparwar A, Mueller-Hennessen M, Weichenhan D, Plass C, Weis T, Backs J, Wuerstle M, Keller A, Katus HA, Posch AE. Epigenome-wide association study identifies cardiac gene patterning and a novel class of biomarkers for heart failure.Circulation. 2017; 136:1528–1544. doi: 10.1161/CIRCULATIONAHA.117.027355.LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Ammirati E, Buono A, Moroni F, Gigli L, Power J, Ciabatti M, Garascia A, Adler E and Pieroni M (2022) State-of-the-Art of Endomyocardial Biopsy on Acute Myocarditis and Chronic Inflammatory Cardiomyopathy, Current Cardiology Reports, 10.1007/s11886-022-01680-x, 24:5, (597-609), Online publication date: 1-May-2022. Schroeter M, Klingel K, Korsten P, Hasenfuß G, De Potter T, Vidal-Perez R, Nistor D, Agarwal M and Sunjaya A (2022) Fulminant Lyme myocarditis without any other signs of Lyme disease in a 37-year-old male patient with microscopic polyangiitis—a case report, European Heart Journal - Case Reports, 10.1093/ehjcr/ytac062, 6:3, Online publication date: 2-Mar-2022. Tschöpe C, Ammirati E, Bozkurt B, Caforio A, Cooper L, Felix S, Hare J, Heidecker B, Heymans S, Hübner N, Kelle S, Klingel K, Maatz H, Parwani A, Spillmann F, Starling R, Tsutsui H, Seferovic P and Van Linthout S (2020) Myocarditis and inflammatory cardiomyopathy: current evidence and future directions, Nature Reviews Cardiology, 10.1038/s41569-020-00435-x, 18:3, (169-193), Online publication date: 1-Mar-2021. Yilmaz A, Bauersachs J, Bengel F, Büchel R, Kindermann I, Klingel K, Knebel F, Meder B, Morbach C, Nagel E, Schulze-Bahr E, aus dem Siepen F and Frey N (2021) Diagnosis and treatment of cardiac amyloidosis: position statement of the German Cardiac Society (DGK), Clinical Research in Cardiology, 10.1007/s00392-020-01799-3, 110:4, (479-506), Online publication date: 1-Apr-2021. Emrich T, Hahn F, Fleischmann D, Halfmann M, Düber C, Varga‐Szemes A, Escher F, Pefani E, Münzel T, Schultheiss H, Kreitner K and Wenzel P (2020) T1 and T2 mapping to detect chronic inflammation in cardiac magnetic resonance imaging in heart failure with reduced ejection fraction, ESC Heart Failure, 10.1002/ehf2.12830, 7:5, (2544-2552), Online publication date: 1-Oct-2020. de Sousa L (2020) Endomyocardial biopsy. Do it whenever you need it!, Revista Portuguesa de Cardiologia (English Edition), 10.1016/j.repce.2020.08.001, 39:8, (461-462), Online publication date: 1-Aug-2020. de Sousa L (2020) Biópsia endomiocárdica. Efectuar sempre que necessário!, Revista Portuguesa de Cardiologia, 10.1016/j.repc.2020.07.001, 39:8, (461-462), Online publication date: 1-Aug-2020. Sullivan R, Randhawa V, Stokes A, Wu D, Lalonde T, Kiaii B, Luyt L, Wisenberg G and Dhanvantari S (2019) Dynamics of the Ghrelin/Growth Hormone Secretagogue Receptor System in the Human Heart Before and After Cardiac Transplantation, Journal of the Endocrine Society, 10.1210/js.2018-00393, 3:4, (748-762), Online publication date: 1-Apr-2019. Ammirati E, Veronese G, Cipriani M, Moroni F, Garascia A, Brambatti M, Adler E and Frigerio M (2018) Acute and Fulminant Myocarditis: a Pragmatic Clinical Approach to Diagnosis and Treatment, Current Cardiology Reports, 10.1007/s11886-018-1054-z, 20:11, Online publication date: 1-Nov-2018. March 6, 2018Vol 137, Issue 10 Advertisement Article InformationMetrics © 2018 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.117.030834PMID: 29506992 Originally publishedMarch 6, 2018 Keywordsheart ventriclesmyocardiumcardiomyopathybiopsyPDF download Advertisement SubjectsCardiomyopathyHeart FailureInflammatory Heart Disease
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